Epidemiology, Real-World Treatment, and Economic Burden of Waldenström Macroglobulinemia: A Comprehensive Analysis Based on Anonymized Claims Data Between 2010 and 2022.

Objectives: This study aimed to provide evidence on the epidemiology, real-world treatment patterns, overall survival, and economic burden of Waldenström macroglobulinemia (WM).

Methods: A retrospective analysis of an anonymized large German claims database from January 1, 2010, to June 30, 2022, identified incident WM cases based on a 12-month diagnosis-free period before the first confirmed WM diagnosis (ICD-10-GM code C88.0).

Chemotherapy-free combination of ibrutinib and obinutuzumab for untreated advanced follicular lymphoma: results of a phase II study from the German Lymphoma Alliance.

Immunochemotherapy induces long-term response in patients with follicular lymphoma. However, toxicity of chemotherapy remains a relevant challenge. The Bruton's tyrosine kinase inhibitor ibrutinib has shown significant activity in patients with indolent B-cell lymphoma.

Report of Consensus Panel 3 from the 12th International Workshop on Waldenstrom's Macroglobulinemia on the management of patients with high-risk disease.

The Consensus Panel 3 (CP3) of the 12th International Workshop on Waldenström macroglobulinemia (IWWM-12) has reviewed and incorporated current data to make recommendations for the management of patients with high-risk WM (HR-WM). Recognizing the considerable heterogeneity in survival outcomes and identifying a subgroup of patients with a very poor prognosis, the key recommendations from CP3 include: (1) Risk stratifying patients with smoldering WM (SWM) and active (symptomatic) WM at diagnosis (2) Using the degree of i) bone marrow lymphoplasmacytosis, ii) serum beta-2 microglobulin (β2M) elevation, iii) IgM increase, iv) serum albumin decrease and the presence of wild-type MYD88 status markers that adversely dictate the time-to-progression from smoldering to active WM to the define HR-SWM. (3) Among patients with active WM, the presenting parameters: advanced chronological age, low serum albumin, elevated serum lactate dehydrogenase, elevated β2M and the presence of TP53 alterations (TP53 mutation or deletion 17p) unfavorably impact the prognosis and should be utilized to risk-stratify patients into the HR category.

Report of Consensus Panel 2 from the 12th International Workshop on the management of Bing-Neel syndrome in patients with Waldenstrom's Macroglobulinemia.

Consensus panel 2 from the 12th International Workshop on Waldenstrom Macroglobulinemia was tasked with updating the guidelines on the diagnosis and management of patients with Bing-Neel syndrome (BNS). In this panel we have summarized the clinical symptoms that may be present with BNS, discussed the criteria required for diagnosis of BNS, made recommendations for follow-up imaging, and proposed revised guidelines for response assessment in BNS. The key recommendations from the 12th International Workshop on WM (IWWM-12) Consensus panel 2 include: (1) the establishment of zanubrutinib as a standard therapy for treatment of BNS; (2) recommendations on imaging and CSF evaluation during treatment and follow-up of BNS; and (3) revised response criteria in view of new data showing that malignant cells can persist in the CSF of many patients treated with BTK-inhibitors.

Report of Consensus Panel 1 from the 12th International Workshop on the management of patients with IgM and Waldenstrom's Macroglobulinemia related neuropathy.

The IgM-related peripheral neuropathies (IgM-PN) are a group of chronic disorders characterized by the presence of monoclonal IgM that may be associated with one of several diseases affecting the peripheral nerves. In many cases, there is a monoclonal IgM associated with activity against neural targets, leading to progressive peripheral nerve demyelination. Neurological symptoms in this setting can also result from direct invasion of the peripheral or central nervous system by lymphoplasmacytic cells (neurolymphomatosis and Bing-Neel syndrome respectively) or via other mechanisms (for example AL amyloid deposition or cryoglobulinemic vasculitis).

GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration.

Background: GPR15LG, a chemokine-like ligand for the G-protein coupled receptor 15 (GPR15), is abundantly expressed in the gastrointestinal mucosa and inflamed skin. Emerging evidence suggests its involvement in inflammatory disorders and cancers. C-X-C chemokine receptor type 4 (CXCR4) plays a critical role in immune cell trafficking and cancer metastasis.

Report of Consensus Panel 6 from the 12th International Workshop on Waldenstrom's Macroglobulinemia on Diagnosis and Management of Transformed Waldenstrom's Macroglobulinemia.

Histological transformation (HT) in Waldenström's macroglobulinemia (WM) is a rare complication and despite growing literature in the last years, no consensus recommendations exist. Consensus Panel 6 (CP6) of the 12th International Workshop on Waldenström's Macroglobulinemia (IWWM-12) was convened to review the current data on transformed WM and make recommendations on its diagnosis and management. The key recommendations from IWWM-12 CP6 included: (1) in case of suspected HT, tissue biopsy is the gold standard for diagnosis; (2) the initial work-up should comprise FDG-PET/CT for the evaluation of disease extent and, for patients with clinical suspicion or for high-risk patients (CNS-IPI, multiple and/or specific extranodal involvements), cerebrospinal fluid examination and brain MRI; (3) standard dose chemoimmunotherapy (CIT) such as R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone) or R-CHP + polatuzumab vedotin are the preferred front-line regimen; (4) CNS prophylaxis and consolidation with autologous stem cell transplantation (SCT) can be considered according to de novo diffuse large B-cell lymphoma (DLBCL) guidelines; (5) T-cell-engaging therapies (CAR T-cells, bispecific antibodies) should be used in the relapse/refractory setting according to international guidelines for DLBCL and local access to these therapies.

Report of Consensus Panel 4 from the 12th International Workshop on Waldenstrom's Macroglobulinemia on the management of patients with non-IgM lymphoplasmacytic lymphoma.

Approximately 95% of lymphoplasmacytic lymphomas (LPL) are IgM secreting and are characterized as Waldenstrom Macroglobulinemia (WM). Conversely, non-IgM secreting LPL are rare. As part of the 12th International Workshop on WM (IWWM-12), a consensus panel of experts was tasked to develop recommendations for the management and response assessment of non-IgM LPL.

Report of Consensus Panel 5 from the 12th International Workshop on Waldenstrom's Macroglobulinemia on the management of patients with intolerance or resistance to covalent BTK inhibitors.

Over the last decade, covalent Bruton tyrosine kinase (BTK) inhibitors have become a standard option for treating patients with symptomatic Waldenström Macroglobulinemia (WM) in the frontline or relapsed settings. However, the definition of intolerance and resistance to covalent BTK inhibitors has not been established. Understanding the best approaches to managing such patients is crucial to avoiding premature abandonment of effective therapy or pursuing futile therapies unlikely to be effective in controlling symptomatic disease progression.

CXCR4 Inhibition Enhances the Efficacy of CD19 Monoclonal Antibody-Mediated Extermination of B-Cell Lymphoma.

CD19 and CXCR4 are pivotal regulators of B-cell activation and migration, respectively. Specifically, CXCR4 signaling critically influences the dissemination of various malignant B cells through constitutive activation and aberrant expression. This study explores the interaction between CD19 and CXCR4 signaling in the context of B-cell lymphomas, particularly focusing on diffuse large B-cell lymphoma (DLBCL) and Waldenström Macroglobulinemia (WM).

Improving access to chimeric antigen receptor T-cells for refractory or relapsing diffuse large B cell lymphoma therapy in Asia.

Chimeric antigen receptor T-cell (CAR-T)-mediated therapies have shown promising clinical benefit in patients with refractory or relapsing (R/R) diffuse large B-cell lymphoma (DLBCL). However, CAR-T treatment presents challenges such as lack of drug accessibility, financial barriers, variable physician preference or experience, and risk assessment based on patient-specific characteristics. This article thus aims to provide an overview of the CAR-T landscape for R/R DLBCL in Asia, with a focus on identifying barriers to access, from the perspective of Asian and international lymphoma experts.

Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia.

Peripheral neuropathy (PN) is a significant cause of morbidity associated with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of zanubrutinib with ibrutinib in patients with WM. This ad hoc analysis examined treatment outcomes with zanubrutinib or ibrutinib on PN symptoms associated with WM in patients enrolled in ASPEN.

Primary central nervous system lymphomas: EHA-ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.

This EHA-ESMO Clinical Practice Guideline provides key recommendations for managing primary DLBCL of the CNS.The guideline covers clinical, imaging and pathological diagnosis, staging and risk assessment, treatment and follow-up.Algorithms for first-line and salvage treatments are provided.